ThermoGen proposes to develop a therapeutic bioreactor able to inactivate bilirubin. The reactor will be based on a thermo-stable bilirubin degrading enzyme produced from a gene cloned from a thermophilic organism. The bioreactor will be able to de-toxify bilirubin by extracorporeal or intercorporeal treatment of blood of patients suffering from liver dysfunction. During Phase I, ThermoGen will systematically screen a large variety of gram negative and gram positive prokaryotic thermophilic organisms for the presence of bilirubin degrading enzymes (preferably oxidases). The screening method is based on a simple spectrophotometric assay which can distinguish between the substrate and its degradation products. The cloning of bilirubin degrading genes from the identified organisms will be accomplished by screening genomic banks in Escherichia coli for the presence of bilirubin modifying enzyme activities. Phase II will aim for the completion of the cloning of the identified genes, their overexpression in suitable hosts, the purification of the protein products and the evaluation of their performance in a variety of prototype bioreactors and as pigment gallstone solubilizaing agents. Phase III will be devoted in the development of FDA approved bioreactors and enzyme preparations for extracorporeal treatment of jaundice.